Regulatory workflow for Registration of Biosimilar products in Egypt

1. Regulatory workflow for Registration of Biosimilar products in Egypt Presented by: Dr/Mona Saleh BiologicalsRegistration Directorate Central Administration for Pharmaceutical Affairs www.eda.mohealth.gov.egbiosimilars@eda.mohealth.gov.eg

2. Topics discussed in the presentation • Establishment History • Mandate Legal Frame Work • Structure of regulatory bodies • Biologicals in Egypt • Similar Biological products • Development of a Biosimilar product • Registration of a Biosimilar Product • Reference guidelines

3. Establishment History • Presidential decree (398/1995) For NORCB establishment. • Presidential Decree (244/2009) executive aspect for NORCB functions. • Administrative decree (16/2009) Establishment of Biological Products Registration Department • Administrative decree (3/2009) Establishment of Biological Products Inspection Directorate • Ministerial Decree (297/2009) Rules & procedures for Registration of Biological products , vaccines, serums & blood derivatives.

4. Mandate Legal Frame work • Pharmacy Law (127/55) Specially Article 58 , 59 ,60 ,61. • Ministerial Decree (95/2005) Assignment responsibility of approving clinical protocols to the Ethics committee of clinical research • Ministerial Decree (297/2009) Rules & procedures for Registration of Biological products , vaccines, serums & blood derivatives. • Ministerial Decree (26/2009) For the charges(fees) rendered for CAPA services. • Ministerial Decree (399/2010) Assignment responsibility of approving protocol & following up the process of clinical trials to NORCB • Ministerial Decree (632/2010) Instruction of evaluation working parties of biological

5. Structure of regulatory bodies Minister of Health Minister Assistant for Pharmaceutical Affairs National Organization for Research & Control of Biological “NORCB” Central Administration for Pharmaceutical Affairs “CAPA” General Inspection Directorate General Registration Directorate Biological products Inspection Directorate Biological Products Registration Directorate

6. Biologicals in Egypt

7. Biologicals in Egypt Classes of Biological products Scope of this presentation is All Biological product Classes other than Blood Products and their recombinant analogues, Vaccines and Sera • Blood derived products • Vaccines & Sera • Epoetins • Interferons • Heparins • Monoclonal Antibodies • Cytokines • Hormones • Insulins • Miscellaneous

8. Biosimilars Biosmilar product is defined as: Biological product (other than blood derived products and their recombinant analogues, vaccines and sera) having the same active substance, dosage form, Strength and route of administration of a reference biological product and has proven through a comparability program that its quality, safety and efficacy is equivalent to a reference biological product when prescribed in a claimed indication

9. Development of a similar biological product

10. Reference Vs. Biosimilar Biosimilar Reference

12. How to develop a biosimilar product Step wise Biosimilar development process: Comparability exercise is part of the development process of the biosimilar product

13. How to develop a biosimilar product continue Data Collection

14. How to develop a biosimilar product (cont.) Reference selection • A single reference product must be used for all comparability exercises during the development process (i.e. quality, safety and efficacy). • The reference product should be justified by the manufacturer of the biosimilar product according to the following criteria:

15. How to develop a biosimilar product (cont.) Reference selection (cont.) The Reference product should be either licensed in Egypt Or Licensed and widely Marketed in a reference country for at least 4 years

16. Registration of a biosimilar product

17. Final dossier approach (Imported product)

18. Final dossier approach (cont.) CAPA Biological Registeration Directorate Front Office Required Docs Company Approval DisApproval Time Line  15 Working Days

19. Final dossier approach (cont.) CAPA Pricing Committee Required Docs Company Price Time Line  60 Working Days

20. Final dossier approach (cont.) CAPA Biological Registeration Directorate • SMFs, M.P & process validation (inspection department) • Stability studies (stability committe) • M2 • (Biologicals evaluation committee)) • PSUR, RMP & DDPS (PVC) • M3,M4, M5 (NORCB) Complete CTD Company Time Line  60 Working Days

21. Final dossier approach (cont.) CAPA Biological Registeration Directorate • (EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack) • Technical Committee Submission • Issue Registration license Time Line  60 Working Days

22. Stepwise approach (Local products)

23. Stepwise approach (Local Products) (Cont.)

24. Stepwise approach (Local Products) (Cont.) CAPA Biological Registeration Directorate Front Office Required Docs Company Approval DisApproval Time Line  15 Working Days

25. Stepwise approach (Local Products) (Cont.) CAPA Pricing Committee Required Docs Company Price Time Line  60 Working Days

26. Stepwise approach (Local Products) (Cont.) CAPA Biological Registeration Directorate 1- ASMF 2- SMF of API Company • Technical Committee Submission SMF of API • CAPA • Biological • Inspection • Directorate ASMF NORCB • (Finished product manufacturing & Control • – perform Stability studies – preclinical studies) Time Line  60 Working Days

27. Performing Clinical trials • Supervising the process by NORCB Stepwise approach (Local Products) (Cont.) DuringThe 3 Years CMC, Preclinical, Clinical Protocal CAPA Biological Registeration Directorate Company • Clinical protocol evaluation (Ethics committee at M.O.H & NORCB • M.P & process validation Evaluation (inspection department) CAPA • Stability evaluation (stability committee) • Charact. & Anal. procedure evaluation at NORCB (registration analysis certificate) • Preclinical studies evaluation (NORCB) Approval

28. Stepwise approach (Local Products) (Cont.) • RMP & DDPS (PV center) • M1 evaluation (Front office department) • Clinical studies evaluation (Biologicals evaluation committee) CAPA Biological Registeration Directorate Complete CTD Company Time Line  60 Working Days

29. Stepwise approach (Local Products) (Cont.) CAPA Biological Registeration Directorate • (EWP decision, PVR, Stability R, TAR, Analysis report, Insert, Pack) • Technical Committee Submission • Issue Registration license Time Line  60 Working Days

30. Re-registration

31. Reference guidelines Global: WHO- GUIDELINES ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS (SBPs) ICH guidelines ICH - Pre-clinical safety Evaluation of Biotechnology-derived pharmaceuticals S6 ICH- General consideration for clinical trials E8 ICH- Statistical principles for clinical trials E9 ICH- Quality of Biotechnological products: Stability testing of Biotechnological/Biological products Q5C ICH- Derivation and characterization of cell substrates used for production of Biotechnological/Biological products Q5D ICH- Viral safety evaluation of Biotechnology products derived from cell lines of human and Animal origin Q5A ICH- Development and manufacture of drug substances (chemical entities and biotechnological/biological entities Q11

32. Reference guidelines EMA-Overarching biosimilar guidelines EMA- Product-specific biosimilar guidelines EMA- Other guidelines relevant for biosimilars EMA- Scientific Guidelines on Biological Drug substances EMA- Scientific Guidelines on Biological Dug Products FDA- Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product FDA- Scientific Considerations in Demonstrating Biosimilarity to a Reference Product CDSCO- Indian Biosimilars Guidelines

33. Thank You